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Review
. 2016 Feb 28;22(8):2441-59.
doi: 10.3748/wjg.v22.i8.2441.

Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer (V体育2025版)

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Review

Peroxisome proliferator activated receptors at the crossroad of obesity, diabetes, and pancreatic cancer

Simone Polvani (V体育平台登录) et al. World J Gastroenterol. .

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer death with an overall survival of 5% at five years. The development of PDAC is characteristically associated to the accumulation of distinctive genetic mutations and is preceded by the exposure to several risk factors. Epidemiology has demonstrated that PDAC risk factors may be non-modifiable risks (sex, age, presence of genetic mutations, ethnicity) and modifiable and co-morbidity factors related to the specific habits and lifestyle VSports手机版. Recently it has become evident that obesity and diabetes are two important modifiable risk factors for PDAC. Obesity and diabetes are complex systemic and intertwined diseases and, over the years, experimental evidence indicate that insulin-resistance, alteration of adipokines, especially leptin and adiponectin, oxidative stress and inflammation may play a role in PDAC. Peroxisome proliferator activated receptor-γ (PPARγ) is a nuclear receptor transcription factor that is implicated in the regulation of metabolism, differentiation and inflammation. PPARγ is a key regulator of adipocytes differentiation, regulates insulin and adipokines production and secretion, may modulate inflammation, and it is implicated in PDAC. PPARγ agonists are used in the treatment of diabetes and oxidative stress-associated diseases and have been evaluated for the treatment of PDAC. PPARγ is at the cross-road of diabetes, obesity, and PDAC and it is an interesting target to pharmacologically prevent PDAC in obese and diabetic patients. .

Keywords: Adiponectin; Adipose tissue; Inflammation; Insulin; Leptin; Metformin; Nuclear receptor; Pancreatic cancer; Thiazolidinediones. V体育安卓版.

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Figure 1
Figure 1
Effects of peroxisome proliferator-activated receptor-γ on diabetes, obesity, and pancreatic ductal adenocarcinoma. The nuclear receptor PPARγ may directly inhibit tumor growth and metastatization and it is implicated in PSC activation. PPARγ activation may increase insulin secretion and production in β-cells, and may increase insulin-sensitivity in peripheral tissue. PPARγ induces differentiation of pre-adipocytes in new small adipocytes that are more insulin-sensitive and produce lower amount of inflammatory adipokines. Finally, PPARγ may directly and indirectly (modulating adiponectin and leptin levels) inhibit inflammation altering the level of adiponectin and leptin. FFA: Free fatty acids; PPARγ: Peroxisome proliferator-activated receptor-γ; PSC: Pancreatic stellate cells.

References (VSports注册入口)

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